Eravacyline is a tetracycline antibiotic that has demonstrated broad spectrum activity against a wide variety of multi-drug resistant Gram-negative, Gram-positive and anaerobic bacteria in humans. In Phase I and Phase II clinical trials, eravacycline also demonstrated a favorable safety and tolerability profile. In view of its attractive pharmacological profile, synthetic routes to eravacycline and, in particular, synthetic routes that result in suitable quantities of eravacycline for drug development and manufacturing, are becoming increasingly important.
As described in International Publication No. WO 2010/017470, eravacycline is conveniently synthesized from 7-fluorosancycline, another tetracycline. 7-Fluorosancycline can be synthesized, in turn, from commercially available 7-aminosancycline or a protected derivative thereof. However, very few procedures for the conversion of C7-amino-substituted tetracyclines, such as 7-aminosancycline, to C7-fluoro-substituted tetracyclines, such as 7-fluorosancycline, have been reported, and those that have are not suitable to be deployed at production-scale.
Therefore, there is a need for improved processes, particularly improved production-scale processes, for converting C7-amino-substituted tetracyclines to C7-fluoro-substituted tetracyclines.